Studies of the candidate genes TGFB2, MSX1, TGFA, and TGFB3 in the etiology of cleft lip and palate in the Philippines

• Published in: The Cleft palate-craniofacial journal Vol. 34; no. 1; pp. 1 - 6
• Main Authors: LIDRAL, A. C, MURRAY, J. C, BUETOW, K. H, BASART, A. M, SCHEARER, H, SHIANG, R, NAVAL, A, LAYDA, E, MAGEE, K, MAGEE, W
• Format: Journal Article
• Language: English
• Published: Chapel, Hill, NC American Cleft Palate-Craniofacial Association 1997
• Subjects: Alleles; Base Sequence; Biological and medical sciences; Case-Control Studies; Chromosome Mapping; Chromosomes, Human, Pair 14 - genetics; Cleft Lip - genetics; Cleft Palate - genetics; Dentistry; Environment; European Continental Ancestry Group - genetics; Female; Genes, Homeobox - genetics; Genetic Linkage; Genetic Predisposition to Disease; Genetic Variation; Homeodomain Proteins - genetics; Humans; Male; Medical sciences; Molecular Sequence Data; MSX1 Transcription Factor; Non tumoral diseases; Otorhinolaryngology. Stomatology; Philippines; Population Surveillance; Syndrome; Transcription Factors; Transforming Growth Factor alpha - genetics; Transforming Growth Factor beta - genetics; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Asia; Philippine Islands; Philippines; Human; Stomatology; Transforming growth factor β; Cytokine; Cleft; Case control study; Congenital disease; Polymerase chain reaction; Lip; Gene; Malformation; Polypeptide; Etiology; Oral cavity disease; Transforming growth factor α; Palate; Molecular biology; Face; Homeobox sequence; Growth factor
• ISSN: 1055-6656; 1545-1569
• DOI: 10.1597/1545-1569(1997)034<0001:SOTCGT>2.3.CO;2

Population-based candidate-gene studies can be an effective strategy for identifying genes involved in the etiology of disorders where family-based linkage studies are compromised by lack of access to affected members, low penetrance, and/or genetic heterogeneity. We evaluated association data for four candidate genes using a population from the Philippines that is genetically separate from previously studied Caucasian populations. Case ascertainment was made possible by collaboration with Operation Smile, a volunteer medical organization, which facilitated identification of a large number of cases for study. A new allelic variant of transforming growth factor-beta 3 was identified to use in these studies. After exclusion of syndromic cases of cleft lip and palate, no evidence for association with previously reported allelic variants of transforming growth factor-beta 2 (TGFB2), homeobox 7 (MSX1), or transforming growth factor-alpha (TGFA), or with the new TGFB3 variant was detected. Previous association studies using Caucasian populations of nonsyndromic cleft lip and/or palate (CL/P) and cleft palate only (CPO) have strongly suggested a role for TGFA in the susceptibility of clefting in humans. Exclusion of significant association in a non-Caucasian population for TGFA suggests that TGFA plays less of a role than it does in Caucasians. This may be due to multiple or different genetic and/or environmental factors contributing to the etiology of this most common cranio-facial anomaly in the Philippine population.